Instructions for Trifas 10 tablets 10 mg No. 30
Composition
active ingredient: torasemide
1 tablet contains torasemide 10 mg;
Excipients: lactose monohydrate, corn starch, colloidal anhydrous silicon dioxide, magnesium stearate.
Dosage form
Pills.
Main physicochemical properties: white, round, flat tablets with beveled edges and a score line on one side. The tablet can be divided into two equal parts.
Pharmacotherapeutic group
Diuretics. Highly active diuretics.
ATX code C03C A04.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Torasemide acts as a saluretic, its action is associated with inhibition of renal absorption of sodium and chlorine ions in the ascending limb of the loop of Henle.
Pharmacodynamic effects
In humans, the diuretic effect rapidly reaches its maximum within the first 2–3 hours after intravenous and oral administration, respectively, and remains constant for almost 12 hours. In healthy volunteers, a dose-proportional increase in diuresis (loop diuretic activity) was observed in the dose range of 5–100 mg. An increase in diuresis was observed in cases where other diuretics, such as distally acting thiazide diuretics, no longer had the desired effect, for example in renal failure. Due to this mechanism of action, torasemide leads to a decrease in edema. In heart failure, torasemide reduces the manifestations of the disease and improves myocardial function by reducing pre- and afterload.
After oral administration, the antihypertensive effect of torasemide develops gradually, starting from the first week after the start of treatment. The maximum antihypertensive effect is achieved no later than 12 weeks. Torasemide reduces blood pressure by reducing total peripheral vascular resistance. This effect is explained by the normalization of disturbed electrolyte balance, mainly by reducing the increased activity of free calcium ions in the muscle cells of arterial vessels, which was found in patients suffering from arterial hypertension.
This effect is likely to reduce increased contractility and/or vascular responses to endogenous vasopressor substances, such as catecholamines.
Pharmacokinetics.
Absorption and distribution
After oral administration, torasemide is rapidly and almost completely absorbed. Peak serum concentrations are reached within 1–2 hours. Bioavailability is approximately 80–90%. Under conditions of complete absorption, the maximum first-pass effect does not exceed 10–20%. According to two studies, food reduces the rate (dynamic component) of torasemide absorption (decreases Cmax and increases tmax), but does not affect overall absorption. The binding of torasemide to plasma proteins is more than 99%, and its metabolites M1, M3, and M5 are 86%, 95%, and 97%, respectively. The apparent volume of distribution (Vz) is 16 liters.
Metabolism
In humans, torasemide is metabolized to form three metabolites, M1, M3, and M5. There is no evidence of the existence of other metabolites. Metabolites M1 and M5 are formed by stepwise oxidation of the methyl group of the phenolic ring to carboxylic acid. Metabolite M3 is formed by hydroxylation of the phenolic ring. Metabolites M2 and M4, identified in animal studies, have not been identified in humans.
Breeding
The terminal half-life (t1/2) of torasemide and its metabolites in healthy volunteers is 3-4 hours. The total clearance of torasemide is 40 ml/min, renal clearance is approximately 10 ml/min. In healthy volunteers, approximately 80% of the administered dose is excreted in the urine as torasemide and its metabolites in the following percentage ratio:
torasemide - approximately 24%, metabolite M1 - approximately 12%, metabolite M3 - approximately 3%, metabolite M5 - approximately 41%. The main metabolite M5 has no diuretic effect. The active metabolites M1 and M3 together account for approximately 10% of the total pharmacokinetic effect. In renal failure, the total clearance and half-life of torasemide do not change, and the half-life of M3 and M5 is prolonged. However, the pharmacodynamic profile remains unchanged. The severity of renal failure does not affect the duration of action. Torasemide and its metabolites are practically not removed by hemodialysis and hemofiltration. In patients with impaired liver function or heart failure, the half-life of torasemide and metabolite M5 is slightly prolonged. The ratio of unchanged torasemide and its metabolites excreted in the urine is practically the same as in healthy volunteers. Therefore, accumulation of torasemide and its metabolites does not occur.
Linearity
Torasemide and its metabolites exhibit linear dose-dependent kinetics, meaning that their maximum plasma concentration and area under the pharmacokinetic curve increase proportionally with dose.
Indication
Treatment and prevention of recurrence of edema and/or effusions caused by heart failure.
Contraindication
Hypersensitivity to the active substance, sulfonylurea drugs, or any of the excipients of the medicinal product.
Renal failure with anuria.
Hepatic coma or precoma.
Arterial hypotension.
Hypovolemia.
Hyponatremia.
Hypokalemia.
Significant urinary incontinence, for example due to prostatic hypertrophy. Breastfeeding.
Interaction with other medicinal products and other types of interactions
Combinations not recommended
Torasemide, especially in high doses, may enhance the ototoxic and nephrotoxic effects of aminoglycoside antibiotics, such as kanamycin, gentamicin, tobramycin and cytostatics - active platinum derivatives, as well as the nephrotoxic effects of cephalosporins. With the simultaneous use of torasemide and lithium preparations, an increase in the concentration of lithium in the blood plasma is possible, which may lead to increased exposure to lithium and the manifestation of adverse reactions.
Combinations of drugs that require caution
Torasemide enhances the effect of other antihypertensive agents, in particular angiotensin-converting enzyme inhibitors, which may cause excessive lowering of blood pressure during their simultaneous use. When using torasemide simultaneously with digitalis drugs, potassium deficiency caused by the use of diuretics may lead to an increase and strengthening of the side effects of both drugs. Torasemide may reduce the effectiveness of antidiabetic agents. Probenecid and non-steroidal anti-inflammatory drugs (e.g. indomethacin, acetylsalicylic acid) may inhibit the diuretic and antihypertensive effects of torasemide. When treated with salicylates in high doses, torasemide may increase their toxic effect on the central nervous system. Torasemide may enhance the effect of theophylline, as well as the effect of curare-like drugs on muscle relaxation. Laxatives, as well as mineralocorticoids and glucocorticoids, may increase the potassium loss caused by torasemide. Torasemide may reduce the vasoconstrictor effect of catecholamines, such as epinephrine and norepinephrine. When used simultaneously with cholestyramine, the absorption of torasemide and, accordingly, its expected effectiveness may be reduced.
Application features
Torsemide should not be prescribed in the following cases:
gout;
cardiac arrhythmias, such as sinoatrial block, atrioventricular block of the 2nd and 3rd degrees);
pathological changes in acid-base metabolism;
concomitant therapy with lithium, aminoglycosides, or cephalosporins;
pathological changes in the blood picture, such as thrombocytopenia or anemia in patients without renal failure;
renal dysfunction caused by nephrotoxic substances;
children and adolescents under 18 years of age.
Due to the fact that during treatment with torasemide an increase in blood glucose concentration may occur, patients with latent and overt diabetes mellitus should be regularly monitored for carbohydrate metabolism. Especially at the beginning of treatment and in the case of elderly patients, special attention should be paid to the appearance of symptoms of hemoconcentration and symptoms of electrolyte loss. With prolonged use of torasemide, regular monitoring of electrolyte balance, in particular serum potassium, is required. The level of glucose, uric acid, creatinine and lipids in the blood should also be regularly monitored. In addition, the general blood picture (erythrocytes, leukocytes, platelets) should be regularly monitored.
Consequences of misuse as doping
The use of the drug Trifas® 10 may cause a positive doping test result. It is impossible to predict the impact on health if the drug Trifas® 10 is used incorrectly, i.e. for doping purposes, - in this case, harm to health cannot be ruled out.
Excipients
Trifas 10 contains lactose, therefore patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not use this medicine.
Use during pregnancy or breastfeeding
Lactation. It is currently not known whether torasemide or its metabolites are excreted in human or animal breast milk. A risk to the neonate/infant cannot be excluded. Therefore, torasemide is contraindicated during lactation (see section 4.3). A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Trifas® 10 taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility: No studies have been conducted on the effect of torasemide on fertility in humans. No such effect of torasemide was observed in animal experiments.
Ability to influence reaction speed when driving vehicles or other mechanisms
Even when used properly, torasemide may adversely affect the reaction rate when driving or operating machinery. This primarily applies to the beginning of treatment, the period of increasing the dose of the drug, changing the drug, prescribing concomitant therapy and drinking alcohol. Therefore, special care should be taken when driving or operating machinery when using torasemide.
Method of administration and doses
Swelling and/or effusions caused by heart failure.
Adults.
Treatment should be initiated with a daily dose of 5 mg torasemide, which is equal to ½ tablet of Trifas® 10. This dose is usually considered a maintenance dose.
The tablet can be divided into two parts as follows:
Hold the tablet with the index fingers and thumbs of both hands with the score line facing up, and by pressing down with your thumbs along the score line, break the tablet.
If the daily dose of 5 mg is insufficient, a daily dose of 10 mg of torasemide is prescribed. Depending on the severity of the patient's condition, the daily dose can be increased to 20 mg per day.
Special patient groups
Elderly patients. No special dose adjustment is required. However, no studies have been conducted to compare the effects of the drug in young and elderly patients.
Patients with hepatic insufficiency. Torsemide is contraindicated in patients with hepatic coma or pre-coma (see section "Contraindications"). Treatment of this category of patients should be carried out with caution, as an increase in plasma concentrations of torasemide is possible (see section "Pharmacokinetics").
Method of application
Tablets should be taken on an empty stomach, with a small amount of liquid. The bioavailability of torasemide does not depend on food intake.
Trifas 10 is usually used for a long time or until the severity of edema decreases.
Children.
The safety and efficacy of Trifas® 10 in children and adolescents under 18 years of age have not been established. Therefore, torasemide should not be used in children and adolescents (under 18 years of age) (see section "Special warnings and precautions for use").
Overdose
Symptoms of intoxication. Typical symptoms are unknown. Overdose may cause excessive diuresis, including the risk of excessive loss of water and electrolytes, drowsiness, confusional state, symptomatic arterial hypotension, circulatory collapse and digestive disorders.
Treatment of overdose. Specific antidote is unknown. Symptoms of intoxication usually disappear when the dosage is reduced and the drug is discontinued and with appropriate fluid and electrolyte replacement (blood electrolyte levels should be monitored). Torasemide is not removed from the blood by hemodialysis.
Treatment for hypovolemia: fluid replacement.
Treatment for hypokalemia: prescribing potassium supplements.
Treatment in case of circulatory collapse: place the patient in the supine position and, if necessary, prescribe symptomatic therapy.
Anaphylactic shock (immediate measures). At the first appearance of skin reactions (such as, for example, urticaria or redness of the skin), the patient's agitated state, headache, sweating, nausea, cyanosis, venous catheterization should be performed; the patient should be placed in a horizontal position with raised legs, ensure free air flow, and administer oxygen. If necessary, further intensive care measures should also be used (including the administration of epinephrine, glucocorticoids, and replacement of circulating blood volume).
Adverse reactions
Below are the side effects that may occur during treatment with the drug Trifas® 10.
The following frequency of adverse reactions was used to assess their occurrence:
very common: ≥1/10;
common: from ³1/100 to <1/10;
sometimes: from ³1/1,000 to <1/100;
rare: from ³1/10,000 to <1/1,000;
very rare: <1/10,000.
Unknown: cannot be estimated from the available data.
From the blood and hematopoietic system: Very rare: hemoconcentration, thrombocytopenia, erythropenia and/or leukopenia (see section "Special warnings and precautions for use").
Metabolism/electrolytes: Common: increased metabolic alkalosis, hyperkalemia, hypokalemia with concomitant low-potassium diet, vomiting, diarrhea, after excessive use of laxatives, and in patients with chronic liver dysfunction. Depending on the dosage and duration of treatment, disturbances of water and electrolyte balance, e.g. hypovolemia, hypokalemia and/or hyponatremia, are possible (see section "Special instructions").
Nervous system disorders: Common: headache, dizziness (especially at the beginning of treatment). Uncommon: paresthesia. Very rare: syncope, cerebral ischemia, confusion.
On the part of the organs of vision. Very rare: visual impairment.
From the side of the organs of hearing and labyrinth. Very rare: tinnitus, hearing loss.
Cardiac system: Very rare: myocardial ischemia, arrhythmia, angina pectoris, acute myocardial infarction.
Vascular disorders: Very rare: thromboembolic complications, arterial hypotension, as well as circulatory disorders in the heart and disorders of the central circulation.
Gastrointestinal disorders: Common: Gastrointestinal disorders (e.g. loss of appetite, stomach pain, nausea, vomiting, diarrhoea, persistent constipation), especially at the beginning of treatment. Uncommon: Dry mouth. Very rare: Pancreatitis.
Hepatobiliary disorders: Common: increased concentration of certain liver enzymes (gamma-glutamyl transpeptidase) in the blood.
Skin and subcutaneous tissue disorders: Very rare: allergic reactions (e.g. itching, rash, photosensitivity), severe skin reactions.
Musculoskeletal and connective tissue disorders: Common: muscle spasms (especially at the beginning of treatment).
From the kidneys and urinary tract. Sometimes: in case of impaired urination (for example, with prostatic hypertrophy), increased urine production may be accompanied by urinary retention and bladder distension.
General disorders and administration site conditions: Common: fatigue, general weakness (especially at the beginning of treatment).
Laboratory data: Common: increased concentration of uric acid and lipids (triglycerides, cholesterol) in the blood (see section "Special warnings and precautions for use").
Sometimes: increased concentration of urea and creatinine in the blood (see section "Special instructions").
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after a medicinal product has been authorised plays an important role. This allows for continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.
Expiration date
3 years.
Storage conditions
No special storage conditions are required. Keep out of the reach of children.
Packaging
10 tablets in a blister; 3 or 5 or 10 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
BERLIN-CHEMI AG.
Location of the manufacturer and its business address
Glienicker Weg 125, 12489 Berlin, Germany.
Applicant
Menarini International Operations Luxembourg S.A.
Applicant's location
1, Avenue de la Gare, L-1611, Luxembourg, Luxembourg
